Immunoexpression of mTOR Pathway Members in Non-Invasive Papillary Urothelial Neoplasms of Bladder
Sehbal Arslankoz, Selcuk Korkmaz, George J Netto, Dilek Ertoy Baydar. Hacettepe University Faculty of Medicine, Ankara, Turkey; Johns Hopkins University School of Medicine, Baltimore, MD
Background: Biomarkers that can predict recurrence in non-invasive papillary urothelial neoplasms are needed. We evaluated expression status of 5 mTOR pathway biomarkers (Pten, phosAkt, mTOR, phos4E-BP1, phosS6) and 2 pathway related markers (p27 and c-myc); aiming to assess their potential role in predicting recurrence in these neoplasms.
Design: Tissue microarrays were constructed from archival tissues obtained from 115 patients with non-invasive papillary urothelial neoplasia of bladder. A total of 347 transurethral biopsies were included in the array comprising 232 follow-up biopsies. The 115 cases consisted of 8 papillary urothelial neoplasia of low malignant potential, 82 low grade papillary urothelial carcinomas and 25 high grade papillary urothelial carcinomas. Immunohistochemistry was performed as previously described by Scultz et al. Cancer 2010. Markers were evaluated for pattern, percentage and intensity of staining. Tumor expression levels were correlated with clinicopathologic parameters. Paired non-neoplastic and neoplastic urothelium were also compared for differences in expression.
Results: Mean follow-up period was 56,60 months (13-258 months). 57/115 tumors (49,6%) had recurrences. Overall, lower phos4E-BP1, p27, mTOR, Pten and phosS6 and higher c-myc expression levels were found in neoplastic urothelium compared to non-neoplastic urothelium. The differences were statistically significant for phos4E-BP1 (p=0,005) and phosS6 (p= 0,003). None of the assessed markers were predictive of recurrence.
Conclusions: Our finding of mTOR pathway members phos4E-BP1 and phosS6 alterations in non-invasive urothelial neoplasms of bladder supports a role in pathogenesis. mTOR markers were not predictive of recurrence in our cohort.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 150, Wednesday Morning